Diagnosis Of Metastatic Breast Cancer Research Articles

Characterizing "collateral damage" in men and women with metastatic breast cancer (mBC) from diverse racial and ethnic backgrounds in New York City.

Patients from diverse racial, ethnic, and socio-economic backgrounds may be particularly vulnerable to experiencing undue social and financial burdens ("collateral damage") from a metastatic breast cancer (mBC) diagnosis; however, these challenges have not been well explored in diverse populations. From May 2022 to May 2023, English- or Spanish-speaking adults with mBC treated at four New York-Presbyterian (NYP) sites were invited to complete a survey that assessed collateral damage, social determinants of health, physical and psychosocial well-being, and patient-provider communication. Fisher's exact and the Kruskal-Wallis rank-sum tests assessed differences by race and ethnicity. Of 87 respondents, 14% identified as Hispanic, 28% non-Hispanic Black (NHB), 41% non-Hispanic White (NHW), 7% Asian American Pacific Islander (AAPI), and 10% other/multiracial. While 100% of Hispanic, NHW, and AAPI participants reported stable housing, 29% of NHB participants were worried about losing housing (p = 0.002). Forty-two percent of Hispanic and 46% of NHB participants (vs. 8%, NHW and 0%, AAPI, p = 0.005) were food insecure; 18% of Hispanic and 17% of NHB adults indicated lack of reliable transportation in the last year (vs. 0%, NHW/AAPI, p = 0.033). Participants were generally satisfied with the quality of communication that they had with their healthcare providers and overall physical and mental well-being were modestly poorer relative to healthy population norms. In our study, NHB and Hispanic mBC patients reported higher levels of financial concern and were more likely to experience food and transportation insecurity compared to NHW patients. Systematically connecting patients with resources to address unmet needs should be prioritized to identify feasible approaches to support economically vulnerable patients following an mBC diagnosis.

Psychosocial and supportive care concerns of young women living with advanced breast cancer: baseline findings from a prospective virtual support intervention study.

Adolescent and young adults (AYAs) with metastatic breast cancer (MBC) experience high physical and psychosocial burdens compounded by a disrupted life trajectory. We sought to determine the psychosocial and supportive care concerns of this population to better understand and address unmet needs. AYAs diagnosed with MBC (18-39years) participating in a prospective interventional study (Young, Empowered, and Strong) at Dana-Farber Cancer Institute completed an electronic survey following enrollment. Measures evaluated sociodemographics, health behaviors, quality of life, and symptoms, among others. We used two-sided Fisher's exact tests to determine associations between concerns (e.g., cancer progression, side effects, lifestyle, finances, fertility) and demographic variables. Among 77 participants enrolled from 9/2020-12/2022, average age at MBC diagnosis and survey was 35.9 (range: 22-39) and 38.3years (range: 27-46), respectively. Most were non-Hispanic white (83.8%) and 40.3% reported their diagnosis caused some financial problems. Many were concerned about fertility (27.0%), long-term treatment side effects (67.6%), exercise (61.6%), and diet (54.1%). Select concerns varied significantly by age, race/ethnicity, and education. Younger women at survey reported greater concern about familial cancer risk (p = 0.028). Women from minority racial/ethnic groups more frequently reported issues talking about their cancer to family/friends (p = 0.040) while those with more education were more frequently concerned with long-term effects of cancer on their health (p = 0.021). Young women living with MBC frequently report psychosocial, health, and cancer management concerns. Tailoring supportive care and communications to address prevalent concerns including disease progression and treatment side effects may optimize wellbeing.

Iterative Development of an Interactive Website to Support Shared Decision-Making in Metastatic Breast Cancer.

Recent treatment advances have resulted in significantly increased survival times following metastatic breast cancer (MBC) diagnosis. Novel treatment approaches-and their related side effects-have changed the landscape of MBC treatment decision-making. We developed a prototype of an online educational tool to prepare patients with MBC for shared decision-making with their oncologists. We describe the five phases of tool development: (1) in-depth, semi-structured qualitative interviews and (2) feedback on storyboards of initial content with patients with MBC and oncology providers. This was followed by three phases of iterative feedback with patients in which they responded to (3) initial, non-navigable website content and (4) a beta version of the full website. In the final phase (5), patients newly diagnosed with MBC (N = 6) used the website prototype for 1week and completed surveys assessing acceptability, feasibility, treatment knowledge, preparation for decision-making, and self-efficacy for decision-making. Participants in Phase 1 characterized a cyclical process of MBC treatment decision-making and identified key information needs. Website content and structure was iteratively developed in Phases 2-4. Most participants in Phase 5 (n = 4) accessed the website 2-5 times. All participants who accessed the website at least once (n = 5) felt they learned new information from the website prototype and would recommend it to others newly-diagnosed with MBC. After using the website prototype, participants reported high preparation and self-efficacy for decision-making. This multiphase, iterative process resulted in a prototype intervention designed to support decision-making for MBC patients.

Abstract PO4-06-05: The prognostic impact of age at diagnosis of metastatic breast cancer according to estrogen receptor status: a single-center, retrospective study

Abstract Background: Young age is associated with poor prognosis and aggressive biology in early breast cancer, especially in luminal subtypes. But the prognostic impact of age in metastatic breast cancer (MBC) is unclear. Also it is known that chemotherapy is more effective in estrogen receptor (ER)-negative tumors than in ER-positive tumors and young patients respond better to chemotherapy. The authors tried to evaluate the impact of age on disease outcome according to ER status. Methods: We collected individual patient data from January 2000 to December 2022 from the Ewha Womans University Mokdong Hospital. Total 419 ER-positive and 238 ER-negative patients who had been treated for MBC were included for analysis. We compared clinical characteristics and overall survival (OS) of patients among three age groups (< 35, 35 to 50 and >50 years) at MBC diagnosis in ER-positive and -negative tumors. Results: The proportion of patients aged < 35, 35-50 and > 50 years was 3.1%, 46.6% and 32.3% in ER-positive tumors, and 2.7%, 14.8% and 18.4% in ER-negative tumors. Although most characteristics of tumors according to age were comparable, bone metastasis was more common in patients aged 35-50 years than the other age groups in ER-positive (51.8% vs. 36.0% in >50 years, P=0.006) and time to first metastasis was shorter in younger patients in ER-negative tumors (72.2% between 6 and 24 months vs. 31.1% in patients >50 years, P=0.003). The median follow-up time was 65 months. Overall survival rate was not different according to age in ER-positive tumors (P=0.909). On the other hands, younger patients had a higher risk of death in ER-negative tumors (P=0.015). In multivariate analysis, young age at MBC diagnosis (< 35years) with short time to metastasis (6 to 24 months), visceral metastasis, triple negative breast cancer was correlated with poor overall survival in ER-negative tumors (P=0.014, HR 1.77). Conclusions: Young age at MBC diagnosis was associated with a higher risk of death in ER-negative tumors, not in ER-positive tumors. These observations may suggest that physicians should consider the impact of age at diagnosis of metastasis and time course of disease in evaluating survival potential and determining a treatment strategy in metastatic breast cancers. Citation Format: Joohyun Woo, Ahrong Ham, Sewon Lee, Ji Eun Lee, Soo Ji Hong, Haena Lee, Sungchan Gwark, Jun Woo Lee, Hyun Goo Kim, Jungmin Jo, Woosung Lim, Byung-In Moon, Sei Hyun Ahn, Hye Ah Lee, Kyoung Eun Lee. The prognostic impact of age at diagnosis of metastatic breast cancer according to estrogen receptor status: a single-center, retrospective study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-06-05.

Abstract PO1-16-12: The McPeak-Sirois Group Breast Metastases Registry

Abstract Background: In 2020, the McPeak-Sirois Group (MPSG), a Quebec-based breast cancer trials consortium, launched a feasibility pilot project to register prospectively cases of metastatic breast cancer (MBC). This Breast Metastases Registry (BMR) had the following objectives: a) to measure real-world progression-free and overall survival; b) to capture real-world evidence in efficacy of novel therapeutic approaches and c) to facilitate the development of clinical research projects in MBC. Methods: The pilot phase was initiated in three major academic hospitals with the intention of testing the feasibility of building a BMR and to assess barriers before extension to other hospitals in the province of Quebec. Funding was obtained through non-profit organizations and the pharmaceutical industry. The project was approved by a research ethics board and informed consent was obtained from each patient. The main inclusion criteria was a MBC diagnosis at the time of enrolment. Metastatic diseases were considered de novo if the metastatic condition was detected at the same time of the primary disease diagnosis or within the following 4 months. The information in the BMR relates to participants’ health status, including but not limited to hospitalizations, diagnoses, medications, medical procedures and imaging, pathology, genetic and laboratory results. In addition to the prospective data, the registry also captures information retrospective to the date of enrollment. Results: Between July 30, 2021 and April 22, 2023, a total of 427 patients were approached by a research nurse and 423 patients enrolled and 4 refused (99.2% participation rate). Approximately one third of the cohort was diagnosed between 2021-2023 (30.3%) while 69.7% were in 2002-2020 timeframe. The majority was either HR+/HER2- (55.3%) or HER2+ (26.9%). The median age at the time of MBC diagnosis was 57 years (Q1-Q3 range: 47-67 years). We observed that 57.9% of patients had a relapsed MBC while de novo MBC comprised 42.1% of the cohort with the highest percentage in the HER2+ group (59.6%). The median time between primary cancer and metastatic disease in those with relapsed MBC is shorter in triple negative breast cancer (28.9 months) compared to 71.4 months in HR+ disease. Among all lines of treatment for metastatic disease, independently of age at time of MBC diagnosis, 21% of patients participated in a clinical trial. Discussion: The pilot project demonstrated the acceptability and feasibility of building a MBC provincial registry as illustrated by the high participation rate (more than 99%). The next step is to expand the registry to other hospital sites in Quebec, however, the main difficulty is having the necessary manpower (oncology registrars) to ensure data entry. Over one third of the MBC patients presented as de novo disease (and more than half of these with HER2+ disease). This proportion of de novo MBC is unusually high and is likely due to a recruitment bias during the pilot phase as data entry was prioritised for de novo diagnoses over MBC at time of recurrence and patients were recruited at any time in their MBC trajectory and not only at the time of their MBC diagnosis. Clinical trial participation was higher in our cohort compared to the usually reported 5% participation rate. This may be due to recruitment bias but needs to be evaluated further. Conclusion: We have found that recruiting patients in a metastatic cancer registry and collecting their real-world data is not only feasible but well received by patients. The limiting factor for expansion to other hospitals is lack of oncology registrars. At maturity, the BMR will be a unique and powerful resource for breast cancer research and will allow researchers and their collaborators to unite their efforts to better understand how stage IV breast cancer is treated and how management of the disease can be improved. The BMR could also have the potential to improve participation in clinical trials and to stimulate clinical research. Citation Format: Julie Lemieux, Danielle Charpentier, Dominique Johnson, Nathalie Bolduc, Caty Blanchette, Claude Nadon, Sarkis Meterissian. The McPeak-Sirois Group Breast Metastases Registry [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-16-12.

Abstract PO2-05-14: Prognosis and clinicopathological characteristics of HER2-negative metastatic breast cancers with low expression of hormone receptors: real world evidence from the French ESME cohort

Abstract Background: HER2-negative breast cancers expressing low (1-9 %) immunohistochemistry levels of hormone receptors (HR, estrogen and progesterone receptors), remain an uncertain category, being considered either as triple negative breast cancers (TNBC) or HR-positive (HR+) tumors across guidelines or approvals. The issues regarding this clinical subgroup are both prognostic, with the need of a better definition of their clinical outcome, as well as predictive. Methods: The ESME database is a French National cohort of all consecutive patients who initiated a first-line treatment for metastatic breast cancer (MBC) from 2008 on, in one of the 18 French Comprehensive Cancer Centers. Patients with HER2-negative (0 to 2+, ISH negative) MBC and known estrogen receptor (ER) and progesterone receptors (PR) expression levels were selected. Primary objective was to evaluate crude overall survival (OS) in HER2-/HR-low (ER and PR 0-9 and not TNBC) MBC pts compared with those with TNBC and HR+ disease defined by ER and PR < 1%, and ER ± PR ≥ 10%, respectively. In these 3 populations, predefined secondary objectives were to evaluate PFS under first line chemotherapy (CT), to describe clinical characteristics and the distribution of genetic abnormalities identified at the time of MBC diagnosis. Results: Out of 30,459 patients in the ESME database initiating their MBC treatment between 01/2008 and 01/2021, 19109 patients (2113 TNBC; 228 HR-low; 16768 HR+) were eligible for this analysis. Median follow-up was 58.0 months (95%CI [56.6; 59.0]). Median OS were 15.7 months [15.0-16.8], 19.1 months [15.5-22.4] and 44.6 months [43.8-45.5] in the TNBC, HR-low and HR+ subgroups, respectively. The multivariable analysis adjusted on age at MBC diagnosis, pathological grade and subtype, metastatic-free interval, number and sites of metastases and HER2 status (0 vs. 1-2+), identified no significant OS difference between HR-low and TNBC subgroups (HR=0.95, 95%CI 0.79-1.14), while HR+ patients had a better OS than TNBC patients (reference) (HR=0.50, 95%CI 0.47-0.53). Of these 19109 pts, 8910 received first-line CT regimen (1960 TNBC; 195 HR-low; 6755 HR+): taxanes-based: 66.7%, anthracyclines-based: 32.9%, capecitabine: 18%. Median PFS under first line CT were 5.3 (5.1-5.6), 5.1 (4.1-6.2) and 10.2 months (9.9-10.6) for TNBC, HR-low and HR+ subgroups, respectively. In the multivariable analysis adjusted on the same variables, the HR-low subgroup had a statistically poorer PFS compared to TNBC (HR=1.24, 95% CI 1.04-1.49). On the other hand, the HR+ subgroup had a better PFS than the TNBC (HR=0.74, 95%CI [0.70; 0.78]). Baseline germline BRCA1 mutations (at MBC diagnosis) were present in 4.5% of the TNBC cases, 2.6% of the HR-low cases, and 0.4% of the HR+ cases. The distribution of germline BRCA2 mutations was more homogeneous between the three groups (0.9% of TNBC cases, 1.3% of HR-low cases and 1.1 % of HR+ cases). Conclusions: In this large cohort, patients with HER2-negative, HR-low MBC seem to share similar general prognosis, oncogenetic features and PFS under standard chemotherapy treatment with TNBC patients. Citation Format: Marie Alexandre, Ludovic Gauthier, Audrey Mailliez, Thibault DE LA MOTTE ROUGE, Thomas Bachelot, Monica Arnedos, Florence Dalenc, Etienne Brain, Jean-Marc Ferrero, Vincent Massard, Isabelle Desmoulins, Marie-Ange Mouret-Reynier, Christelle Levy, Anthony Gonçalves, Marianne Leheurteur, Thierry Petit, Jean-Sébastien Frenel, Lise Bosquet, Suzette Delaloge, William Jacot. Prognosis and clinicopathological characteristics of HER2-negative metastatic breast cancers with low expression of hormone receptors: real world evidence from the French ESME cohort [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-05-14.

Abstract PO2-10-07: Patterns of presentation, treatment and survival for older patients with metastatic breast cancer (MBC): results from a large prospective registry

Abstract Background: The median age of breast cancer diagnosis in the U.S. is 62 years; however, older pts with breast cancer are consistently underrepresented in clinical research. In population-based studies, older pts, particularly those aged 70+, do worse than their younger counterparts at every stage of disease, including stage IV. However, our understanding of patterns of recurrence, treatment patterns, and outcomes for older pts with MBC is limited by a lack of available data. Methods: We identified pts age >60 years seen at least once at a single, NCI-designated cancer center for a diagnosis of MBC between 1999-2022 with 1+ years of follow-up from the time of their metastatic diagnosis. We categorized pts into 5-year age groups (60-65; 66-70; 71-75; 76-80; >80) and two groups of 60-70 and >70. Clinicopathologic characteristics, treatment patterns, reason for treatment discontinuation, and the proportion enrolling on clinical trials were compared by tumor subtype and age group using Chi-Square testing. Median overall survival using Kaplan-Meier method was calculated from the date of initial MBC diagnosis to date of death or last follow-up, examined by tumor subtype and age. Results: The final analytic cohort included 1,115 patients diagnosed with MBC with median follow-up of 2.9 years (1.0-18.5). Median age at MBC diagnosis was 66.3 years (60.0-95.4) and 10% were non-White; disease subtype distribution was the following: 70.7% HR+HER2-, 11.9% HER2+, 17.4% TN. Overall, 22.2 presented with de novo MBC. Presentation of MBC did not vary by ages 60-70 vs. 70+, with no differences in disease characteristics such as grade and disease sites at MBC diagnosis (except for bone). However, the proportion of pts with HR+HER2- disease increased with age, from 69% of MBC in ages 60-70 and 76% in ages >70 (p=.02). In pts with this subtype receiving first-line (1L) therapy (n=783), use of endocrine therapy as 1L (with or without a CDK4/6 inhibitor) increased by age (77.8% in ages 60-65 v. 94.7% in ages >80); use of 1L chemotherapy also varied by age (22.2% in ages 60-65 v. 5.3% in >80). Among pts with HER2+ BC, 89% received a trastuzumab-containing regimen in the 1L setting; in pts with TN MBC, 94% received at least 1L line of chemotherapy. Overall, most pts discontinued 1L therapy for progression, not toxicity, and there was no variation in rates of discontinuation due to toxicity by age with 10.4% noted in both age groups, 60-70 and >70. The proportion of patients receiving 3+ lines of chemotherapy across disease subtype decreased with increasing age (e.g., 54% in ages 60-65 v. 25% in ages >80 among HR+HER2-; 69% in ages 60-65 and 33% in ages >80 among TN MBC). Overall, enrollment on a clinical trial in the MBC setting steadily decreased with older age from 40% in ages 60-65 to 13% in ages >80 (p=.0004). Overall median overall survival differed with increasing age from 4.4 yrs in ages 60-65 to 2.7 yrs in ages >80 (p< 0.005). In descriptive analyses, the proportion of pts alive at 2 yrs was variable. For those ages 60-65, 37.8%, 17.1%, and 42.9% of pts with HR+HER2, TN, and HR-HER2+, respectively were alive at 2 yrs. For those ages >80, 23.7%, 0%, and 0% of pts with HR+HER2-, TN, and, HR-HER2+ disease were alive at 2 yrs. Median survival times were < 2 years for pts with TN regardless of age. Conclusions. In a unique, large prospective cohort of older pts with MBC, we examined detailed information on disease presentation, treatments, and outcomes, lending new information on patterns of care and experiences for older pts with MBC in a modern real-world experience. Limitations include a single center experience and small numbers of older pts with HER2+ and TN disease. Although the oldest pts with MBC had similar disease characteristics as younger pts in our dataset, survival outcomes were poor, particularly for those ages 80+. Therapeutic approaches, likely including improved supportive care, are urgently needed to optimize outcomes in the oldest pts with MBC. Table 1. Outcomes for older pts with MBC Citation Format: Melissa Hughes, Alyssa Patterson, Alexandra Newman, Amanda Higgins, Gregory Kirkner, Janet Files, Molly Skeffington, McKenna Moore, Sarah Strauss, Nicole Kuhnly, Lindsey Crowley, Sara Tolaney, Nancy Lin, Rachel Freedman. Patterns of presentation, treatment and survival for older patients with metastatic breast cancer (MBC): results from a large prospective registry [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-10-07.

Abstract PO4-15-01: A multi-center prospective cohort study to evaluate the presence of circulating tumor cells using the Epic Sciences platform among women with metastatic breast cancer

Abstract Background: The presence of tumor cells (or their components) in the blood of women with a history of early breast cancer has the potential to herald the development of metastatic recurrence at its earliest stages. Such early detection could potentially lead to novel prevention strategies, but it requires a sensitive assay. Objective: To use the Epic Sciences platform to detect and enumerate CTCs in blood samples from patients with an established diagnosis of metastatic breast cancer (MBC), prior to initiation of 1st line systemic therapy in the metastatic setting. Methods: We conducted a multi-center prospective cohort study to evaluate the presence of CTCs using the Epic Sciences platform among patients with a new diagnosis of MBC. Men or women age 18 to 85 were included, irrespective of breast cancer subtype. Patients with a prior or concurrent malignancy whose natural history or treatment had the potential to interfere with the detection of MBC in a liquid biopsy were excluded. A one-time blood draw was performed before patients received any local or systemic therapy in the metastatic setting. In addition, those with recurrent disease must have been off any systemic adjuvant therapy for ≥3 weeks prior to blood collection. Two 5 mL blood samples were obtained for CTC identification and enumeration. CTC identification was based on immunofluorescence analysis using Epic Sciences platform as previously described (Ueno et al 2017). The presence of CTCs was correlated with clinical and pathological features, which were abstracted from medical records and pathology reports. The association between the presence of CTCs and clinical/pathologic characteristics was tested using Fisher’s exact test for categorical variables and t-test or Wilcoxon rank sum tests for numerical variables. All analyses were performed using the R software package. Results: 100 patients were recruited between February 2021 and January 2023 at five academic oncology centres in Ontario and Quebec, Canada. 95 patients had evaluable blood for analysis and 5 did not due to blood age and/or insufficient blood volume. Six patients were excluded after providing a blood sample because tissue biopsy ultimately revealed a 2nd primary tumor (n=4) or benign tissue (n=2). Hence, 89 patients with a clinical diagnosis of MBC and with evaluable blood for CTC analyses were ultimately included in our cohort. The average age of patients was 61 years. Most patients (n=49, 55%) had a prior history of early breast cancer, 38 (43%) had de-novo metastatic disease and prior breast cancer history was unknown for 2 patients. 50 (66%) of patients had visceral metastatic disease. The most common sites of metastases included bone (62%), lung (30%), liver (29%) and lymph nodes (17%). 63 of 89 patients (71%) had detectable CTCs at baseline, prior to any local or systemic treatment in the metastatic setting. The median number of detectable CTCs per 5mL sample was 2 (IQR 8.5) and the range was 0 – 12,798. Twenty nine of 89 (33%) patients had 5 or more CTCs detected per 5ml blood. The proportion of patients with detectable CTCs was numerically highest (n=39/51, 76%) among patients with hormone receptor (HR)+/HER2-ve breast cancer, followed by HER2+ (n=16/22, 73%) and triple negative (n=8/13, 62%) disease. Associations between CTC detection with prior history of early breast cancer, sites of metastatic disease and disease burden will also be presented. Conclusions: Approximately 3 in 4 women with newly diagnosed metastatic breast cancer have detectable CTCs using the Epic Sciences platform prior to initiation of first line systemic therapy. CTCs may be a promising tool for the monitoring of breast cancer recurrence and will be investigated in an ongoing Canadian prospective observational study that aims to elucidate biomarkers of late breast cancer recurrence. Citation Format: Katarzyna Jerzak, Pamela Goodwin, Marguerite Ennis, Christine Brezden-Masley, Nathaniel Bouganim, Mark Basik, Arushi Jain, Giuseppe Di Caro, Rick Wenstrup, Nadine Hartmann, Megan Slade, Ana Elisa Lohmann. A multi-center prospective cohort study to evaluate the presence of circulating tumor cells using the Epic Sciences platform among women with metastatic breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-15-01.

Abstract PO5-04-12: Comparison of chemotherapy efficacy in metastatic lobular vs. ductal breast cancer

Abstract Comparison of chemotherapy efficacy in metastatic lobular vs. ductal breast cancer Background: Invasive lobular carcinomas (ILC) are thought to be less chemo-sensitive than invasive ductal carcinomas (IDC), as reflected by lower rates of pathological complete response following neoadjuvant therapy. In the metastatic setting, evidence regarding chemotherapy (Cx) efficacy is limited. Methods: A retrospective review of prospectively collected data for consecutive patients (pts) with metastatic ILC (mILC) treated at a single institution between 2000 and 2023 was included. Pts with mILC were matched on a 1:2 ratio with a cohort of pts with metastatic IDC (mIDC) by age, era of diagnosis and initial metastatic burden. Primary outcome was efficacy of Cx in mILC vs. mIDC pts as measured by time to next treatment - TTNTc (months (m) between start date of first & second Cx). Key secondary endpoints included differences in efficacy of endocrine therapy between the two groups (as measured by TTNT and outcomes in pts with endocrine resistance (EnR) as defined by ESMO consensus guideline) and overall survival (time from diagnosis of metastatic breast cancer (BC) to death or last follow-up [OS]). Results: 376 pts were included, mILC (122) and mIDC (254) with median age 64y and 62y, respectively. A significantly higher proportion of mILC pts had hormone receptor positive/HER2 negative or lower proportion of triple negative disease (p< 0.0001). Compared to mIDC, mILC pts were more likely to have de novo disease (29% vs. 18%; p=0.02), lower grade (p< 0.0001), received endocrine therapy only (p=0.03) and were less likely to have visceral disease at diagnosis or any time after metastatic diagnosis (20% vs. 45% p< 0.0001, 35% vs. 51% < 0.0004, respectively). Median time to commencing chemotherapy from metastatic diagnosis was longer in mILC pts (5.8 v 2.0 m, p=0.03). There was no significant differences in TTNTc for patients with mILC and mIDC except for those with visceral disease at diagnosis (Table 1). There was no significant difference in TTNTc by histological subtype of mILC (p=0.46) or by choice of first line chemotherapy used (p=0.91). In the entire population, no significant OS difference observed in mILC and mIDC (Table 1). BC outcome was assessed in pts receiving endocrine therapy as first-line treatment (mILC 65, mIDC 102). There was no difference in TTNT (mILC 14.6m vs. mIDC 14.8m). There were no differences in incidence of EnR between the groups. OS was shorter in mILC pts with primary EnR. The presence of primary, secondary or no resistance within each histological group was significantly associated with OS (Table 1). Conclusion: Pts with mILC have a longer time to commencing chemotherapy, but efficacy of chemotherapy is similar to pts with mIDC; irrespective of lobular histologic subtype, first line chemotherapy regimen used and sites of disease, except for those mILC with visceral disease. There was no significant difference in OS between mILC and mIDC pts treated in this single centre study. Efficacy of endocrine treatment when given as first line treatment was similar in both groups with no significant difference when pts were evaluated by presence or absence of endocrine resistance, except for primary EnR, but pt numbers were small in this group. Our results demonstrate equivalent chemotherapy efficacy in pts with mILC as compared to mIDC.

Abstract PO4-05-01: Clinical outcomes of breast cancer and its relationship with access to health care in Brazil: prospective study in HER2 negative/hormone receptor positive metastatic disease - BREAST (BRazilian outcomE for metAStatic breasT cancer)

Abstract Background: Cancer survival is one of the key measures of the effectiveness of cancer services and captures whether people have access to effective treatment. The survival rate of breast cancer in low and middle-income countries is notably different from high-income countries; this disparity in survival reflects limited access to first-line systemic therapy for advanced and metastatic tumors. Recent studies have shown benefit of combining cyclin-dependent kinase 4 and 6 inhibitors (CDK 4/6) with endocrine therapies in hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) advanced or metastatic breast cancer. However, in Brazil, the population has limited access to these drugs, mainly in the public health service. The commercialization of CDK 4/6 inhibitors was only released in the national territory in 2018, but until nowadays it is not accessible for most patients. Objective: The aim of this project is to assess whether patients without private health insurance may experience worse outcomes compared to women with private insurance, primarily due to limited access to a specific class of medication during their treatments. The study seeks to gain insights into the clinical outcomes of patients with HR+ HER2- metastatic breast cancer based on their access to health insurance coverage within a real-world setting. Methods: Multicenter, prospective observational study, with patients divided into two groups: one with patients from the public health system and the second with patients treated at the private service. Whereas that the hazard ratio for the primary outcome in the private system compared to the public health system is like that observed in the PALOMA study (0.58), and that event rates after 18 months of follow-up are also similar (approximately 45% and 35%), then a total of 298 patients will provide the study power of 80%, significance level of 5%. This calculation considers a sample size ratio of 1 patient in the private health system for every 2 patients in the public health system. The inclusion criteria specify women with HR+ HER2- metastatic breast cancer who initiated first-line treatment from 2019. Patients will be followed for 24 months and stratified based on the use or non-use of CDK 4/6 inhibitors. The study was approved by the local ethics committee and registered with Clinical Trials (NCT05559528). Results: A total of 300 patients were evaluated, with 199 (66.3%) in the public health system and 101 (33.7%) in the private service. The mean age was 58 years, and 76.2% were postmenopausal. In terms of metastasis site, 84.7% had non-visceral disease, predominantly with bone metastasis (75.7%), which is an expected characteristic of this type of tumor. The use of CDK 4/6 inhibitors at any point in the treatment of metastatic disease was 7.0% in the public health system versus 90.1% in the private service. As a preliminary outcome, with a median time since the diagnosis of metastatic breast cancer of 22.8 months, a mortality rate of 10% was identified in the public health system group compared to 5% in the private service group. Conclusions: The results of our study highlight the disparity in the treatment of metastatic breast cancer among patients in relation to access to healthcare. Patients dependent on the public health system experience higher mortality rates. These findings are crucial for supporting discussions on improving local policies regarding access to medications that have been proven to enhance the prognosis of these patients. Citation Format: Vanessa Sanvido, Lucíola Pontes, Rachel Machado, Marina Nicola, Jackeline Gomes, Letícia Barbante, Nanci Valeis, Alexandre Cavalcanti, Afonso Nazário. Clinical outcomes of breast cancer and its relationship with access to health care in Brazil: prospective study in HER2 negative/hormone receptor positive metastatic disease - BREAST (BRazilian outcomE for metAStatic breasT cancer) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-05-01.

Abstract PO4-12-10: Sacituzumab Govitecan Toxicity Outcomes In Arab Patients with Metastatic Breast Cancer

Abstract Background: The Arab population is often underrepresented in clinical trials, which limits our knowledge of drug safety and efficacy in this population due to genetic variability that can affect drug metabolism and adverse events (AEs). Sacituzumab govitecan (SG) is approved for metastatic triple negative breast cancer (mTNBC), and recently hormone receptor positive metastatic breast cancer (HR+ MBC). Here we report toxicity outcomes and RDI in Arab population. Methods: A multi-center retrospective study of patients with mTNBC and HR+ MBC treated with SG from January 2021 until May 2023 was conducted. Demographics and clinical variables including site of metastases, prior lines of therapy, relative dose intensity (RDI), adverse events (AEs) were collected. For continuous variables, Mann-U Whitney and Kruskal Wallis tests were used to compare mean, median, standard deviation, and range. For categorical variables, Fisher's exact tests and Pearson Chi-square tests were used. SAS v9.4 was used to perform statistical analysis at a significance level of 0.05. Results: A total of 35 patients was enrolled. The median age at diagnosis of metastatic breast cancer was 39 years interquartile range (IQR) (35, 44). The median age at starting SG was 44.5 years IQR (38,50). The majority of patients (65%) had an Eastern Cooperative Oncology Group performance status (ECOG PS) of 1, (21%) of the patients had an ECOG PS of 0, and (15%) had an ECOG PS of 2. 48.6% received 3 or more lines of prior therapy in the metastatic setting while 51.4% received less than 3 lines of prior therapy in the metastatic setting. 77.1% of patients had 3 or > organs involved with metastatic disease, while 22.9% of patients had < 3 organ involved. The most common metastatic sites were the lung (54.3%), liver (62.9%), bone (68.6%), and brain (45.7%). The median RDI of SG was 100% for a sample of 34 individuals, with one missing value IQR (94%,100%). The rate of overall AEs was (77.1%), with the most common AEs being; neutropenia (44.4%), diarrhea (37.0%), anemia (22.2%), thrombocytopenia (22.2%), nausea (14.8%), and vomiting (7.4%). Garde 3 AEs rate was 34.3%. The most common grade 3 adverse events were diarrhea (11.4%), fatigue (5.7%), and alopecia (2.9%). The rate of treatment interruption and dose reduction due to AEs was 31.4%. Only one patient (2.9%) had to discontinue SG treatment due to adverse events. Conclusion: The study suggests that SG is safe and well-tolerated in young Arab patient population. The sample consisted of relatively young patients, which may reflect a reluctance to prescribe SG to older Arab patients. Caution should be exercised when generalizing the findings due to limitations of the study. Further studies with larger sample sizes are needed to validate these findings and to explore the efficacy of SG in Arab patients with mTNBC and HR+ MBC. Citation Format: Maymouna Altarturi, Kausar Suleman, Adhar AlSayed, Humaid Al-Shamsi, Aydah Alawadhi, Bassam Basuliamn, Sabah Alaklabi. Sacituzumab Govitecan Toxicity Outcomes In Arab Patients with Metastatic Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-12-10.

Abstract PO1-11-03: Women with Metastatic Disease: Modeling a Clear and Well-Defined Announcement Pathway

Abstract Introduction: The announcement of the diagnosis of metastatic breast cancer is a key step in enabling the patient to fully understand her disease and the various treatment options, and thus to be more involved in her management and follow-up. However, according to the « Croyances et réalités 2 » survey conducted in 2021 among 269 French patients with metastatic breast cancer, 38% of them felt that they "did not fully understand" the information given by their doctor during the announcement consultation. Objective: The objective of this work is to model an optimal pathway for the announcement of metastatic breast cancer based on precise guidelines and good coordination between the different actors, in order to ensure that all patients have the necessary information and support. Method: A scientific committee composed of 4 French oncologists from 4 different centers initiated a collaborative process to propose, after discussions, precise guidelines for the announcement of metastatic breast cancer. Results: A set of 13 concrete guidelines were suggested by the expert group (Table 1). The central aspect is to build a specialized and flexible support, adapted to the needs of the patient, without ever hiding the truth about her disease. The announcement process must be adapted to the patient's history (recurrent or immediately metastatic), but also to the organization and resources available in the health care institution. The experts recommend a model of announcement process in two stages, separated by a few days. First, the oncologist announces what the entry into metastatic disease represents, followed by a repeat of the announcement by a nurse trained in the specificities of metastatic breast cancer, in order to have the patient reformulate her understanding of the disease and treatment. In a second phase, a new consultation allows to present the next therapeutic steps and ensure a coordinated intervention of the different health care professionals involved: doctors, nurses, pharmacists and supportive care specialists as needed. The offer of supportive care should be flexible and it is recommended that questionnaires should be made available to the patient to help identify her precise needs. The experts recommend that this second consultation be conducted jointly by an oncologist and a nurse. Subsequently, the town physician and pharmacist must be contacted to ensure the relay in the accompaniment of the patients in partnership with the cancer care center, and thus to ensure a good sharing of information on the patient's follow-up. To help the establishment of this dynamic announcement model, the experts gave advice on implementation: training the professionals involved in the process through theoretical training and role-playing, increasing the amount of time spent on the announcement consultation, and setting up a library of online or physical information materials to share with the patient. Finally, it is recommended that the financing of this process be prepared at the institutional level before its effective implementation in order to ensure its sustainability. Conclusion: Organizing a consultation for the announcement of metastatic breast cancer is essential to optimize the experience of the announcement and support. It must be a structured, funded and coordinated process between different health professionals specially trained for this approach. Table 1: Summary of guidelines for a metastatic breast cancer notification pathway. Citation Format: Florence Dalenc, Séverine Guiu, Marie-Ange Mouret-Reynier, Nathalie Quenel-Tueux. Women with Metastatic Disease: Modeling a Clear and Well-Defined Announcement Pathway [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-11-03.

Abstract PS17-04: Clinical and Genomic Features of ER-Positive/HER2-negative Metastatic Breast Cancer in AURORA Molecular Screening Initiative (BIG 14-01): Mechanisms of Endocrine Therapy Resistance and Implications for Adjuvant Approaches

Abstract Background: Up to 30% of patients (pts) with ER-positive early breast cancers develop metastatic relapse. The molecular differences between endocrine therapy (ET)-sensitive and ET-resistant relapses, as well as the impact of specific adjuvant ET-based therapies, remain unclear. Methods: The AURORA program (NCT02102165) analyzed multi-omics data of paired primary (prim) and metastatic (meta) tumor tissue, along with plasma samples, from 1,156 patients with metastatic breast cancer (MBC). Targeted genome sequencing (TGS), RNA sequencing, and circulating tumor DNA analysis were performed. ET-resistance at MBC diagnosis was defined following the 5th ESO-ESMO ABC Guidelines. Results: We studied 628 pts with metastatic ER+/HER2- disease. Patient´s median age was 56 years, 133 (21%) were premenopausal, 314 (50%) had ET-resistance at recurrence (9% primary, 41% secondary), 132 (21%) had ET-sensitive recurrence, and the rest were ET-naive recurrences or de novo MBC. Adjuvant treatment was aromatase inhibitor (AI) +/- ovarian function suppression (OFS) in 288 (46%) pts, while 159 (25%) had tamoxifen only (+/- OFS). Gene expression correlation significantly differed (p < 0.005) based on ET-resistance in 92 paired samples. ET-sensitive (n=11) and de-novo tumors (n=41) showed higher correlation than primary (n=7) and secondary ET-resistance (n=32), regardless of adjuvant ET type. Prim and meta showed concordance in 91% of IHC subtypes and 62% of intrinsic subtypes. Intrinsic subtype showed 9% of prim luminal tumors switching to meta non-luminal, with 66% of Luminal A switching to Luminal B. Neither IHC nor intrinsic subtype switching was associated with the type of adjuvant ET or ET resistance. Pts with meta non-luminal intrinsic subtype (18%) had worse PFS on CDK4/6i (HR 4.0, 95% CI 1.9-8.7) and OS (HR 3.6, 95% CI 2.0-5.7) than luminal subtypes. TGS was performed in 534 meta (365 before 1L, 305 pairs). In meta before 1L, the dN/dS algorithm revealed selection in 17 genes, including TP53, PIK3CA, and ESR1. Mutations (mut) in ESR1, ERBB2, ERBB3, and RB1 among others, were specifically identified in meta. The incidence of ESR1mut was 3% in prim, 12.6% before 1L, 23.4% after 1L, and 4.7% in meta from ET-naive tumors (Table). Before 1L, ESR1mut was higher after adjuvant AI vs tamoxifen (21% vs. 4%, p< 0.001). ESR1mut incidence varied with ET-resistance (16% primary, 19% secondary, 9% sensitive, 4% ET-naïve/de novo, p< 0.01). Paired samples showed that ESR1mut were mainly acquired events and associated with higher ER mRNA signaling (hallmark estrogen response) compared to ESR1wt (p < 0.05). The agreement between ESR1mut detected in ctDNA and tissue was high before 1L (90%), and slightly lower after 1L (84%). In a multivariate model with relevant clinical factors, ESR1mut were associated with worse OS (HR 1.76, 95% CI 1.2-2.5, p=0.003), independently of TP53 and PIK3CA mutational status. Conclusion: AURORA study sheds light on metastatic tumor alterations acquired under anti-cancer therapy, in ER+/HER2- MBC. We observed a high prevalence of acquired ESR1mut prior to the initiation of first-line therapy, particularly in tumors exposed to adjuvant AI or with primary or secondary ET_resistance. The association of ESR1muts with poorer OS underscores the importance of implementing effective adjuvant ET strategies to prevent the emergence of these mutations. Frequency of driver gene mutations in primary and metastastic tumors before 1st-line treatment according to adjuvant ET and type of ET resistance Table. Citation Format: Angel Guerrero-Zotano, Matteo Benelli, Alexandre Irrthum, David Cameron, Lorenzo Ferrando, Dario Romagnoli, Marta Paoli, Arnau Llinas, Maya Dadiani, Danai Fimereli, Mafalda Oliveira, Carmela Caballero, Thayane Crestani, Elisa Agostinetto, Diogo Martins-Branco, Florentine Hilbers, Einav Gal-Yam, Marija Balic, Fatima Cardoso, Jorge Reis-Filho, Christos Sotiriou, Giuseppe Curigliano, Barbro Linderholm, Evandro de Azambuja, Susan Knox, Cristina Rotaru, Eva Ciruelos, Nancy E Davidson, Giuseppe Viale, Donatienne Taylor, Jean-Luc Canon, Lourdes Calvo, Joan Albanell, Marco Colleoni, Caroline Duhem, Nadia Harbeck, Catherine Herremans, Sibylle Loibl, Sandrine Marreaud, Elsemieke Scheepers, Alice Raimbault, Theodora Goulioti, Andrea Vingiani, Chiara Biagioni, Sebastian Vosberg, Gabriele Zoppoli, Jose Seoane, David Venet, Philippe Aftimos, Martine Piccart. Clinical and Genomic Features of ER-Positive/HER2-negative Metastatic Breast Cancer in AURORA Molecular Screening Initiative (BIG 14-01): Mechanisms of Endocrine Therapy Resistance and Implications for Adjuvant Approaches [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS17-04.

Abstract PO1-23-09: A bedside-to-bench translational analysis demonstrates that NF1 alterations promote CDK4/6 inhibitor (CDK4/6i) resistance in hormone receptor-positive (HR+) metastatic breast cancer (MBC)

Abstract Background: CDK4/6i are part of the standard management of HR+ MBC. The MAPK pathway has been implicated in mediating resistance to CDK4/6 blockade (Wander 2020). A variety of molecular alterations dysregulate MAPK signaling, including NF1 mutations (NF1-MUT) (Wallace 2012), though NF1 has not been implicated in CDK4/6i resistance. To assess this, we analyzed retrospective clinical data from multiple institutions, real-world data (RWD) from the GuardantINFORM database, and preclinical models of HR+ breast tumors. The primary objective of this study was to characterize clinical outcomes of CDK4/6i in patients (pts) with NF1-MUT MBC, and to validate those findings in laboratory models. Methods: Pts with pathogenic (p)NF1-MUT were identified via sequencing of circulating tumor DNA (ctDNA) or tumor tissue. Pathogenic was defined as nonsense, insertion/deletion, frameshift, or oncogenic missense mutations. Progression free survival (PFS) on CDK4/6i was analyzed, and intrinsic resistance was defined as progression < 6 months on 1st line (1L) CDK4/6i or < 3 mo on 2nd line and beyond (2L+). Acquired resistance was defined as PFS >6 mo (1L) or >3 mo (2L+) with a NF1 alteration detected post-progression. RWD from the GuardantINFORM dataset had Guardant360 (G360) ctDNA testing linked with claims data on >37,000 pts with advanced or MBC tested between June 2014 and March 2023. Pts on CDK4/6i within 90 days pre-G360 were stratified as NF1-MUT (n = 28) vs. NF1-non-mutant (NF1-nonMUT) (n = 1133) and analyzed for real-world time-to-next-treatment (rwTTNT) and real-world overall survival (rwOS). Propensity score weighting for age, sex, line of therapy, and year of G360 were used to create a balanced control group. To determine whether NF1 loss-of-function alterations were causal of CDK4/6i resistance, we used CRISPR/Cas9 to delete NF1 in MCF7 breast cancer cells. MCF7 wild-type (WT) and two NF1-knockout (KO) clones were treated with palbociclib ± estrogen deprivation, followed by cell viability assays. MAPK and PI3K/AKT pathway activation were measured by immunoblot analysis. Results: Across 4 institutions, 40 pts with HR+, HER2- MBC expressing pNF1-MUT and prior CDK4/6i were included. The mean age at MBC diagnosis was 56 years, and the majority of pts received no prior treatment in the metastatic setting before CDK4/6i (range 0 - 5 prior lines). Intrinsic or acquired resistance to CDK4/6i was seen in 29/40 (73%) tumors harboring pNF1-MUT. We analyzed pts with baseline pNF1-MUT who received 1L CDK4/6i plus endocrine therapy (n = 13) and found that the median PFS was 7.7 months (range 2 - 18 mo). We next examined GuardantINFORM RWD and discovered a significant difference in rwTTNT and rwOS on CDK4/6i for NF1-MUT (n = 28) vs. weighted NF1-nonMUT (n = 28) tumors. Mean age (62 years) and level of pretreatment (majority 2L+) were similar between the groups. Compared to NF1-nonMUT, NF1-MUT pts had a shorter median rwTTNT on CDK4/6i regimens (4.2 vs. 12.4 mo, weighted log-rank p< 0.0001) and worse rwOS (15.8 vs 45.2 mo, weighted log-rank p=0.016). In MCF7 cells, NF1-KO exhibited a palbociclib IC50 11- to 13-fold higher than NF1-WT controls. In estrogen-deprived media, treatment with 250 nM palbociclib for 6 days reduced MCF7 NF1-WT cell viability 75% but only 5-20% in NF1-KO cells. As expected, phosphorylation of ERK and AKT were strongly induced in NF1-KO cells relative to NF1-WT. Conclusions: Using multicenter clinical and real-world evidence, we demonstrate that NF1-MUT is associated with inferior duration and worse outcomes on CDK4/6i in MBC. Pts with baseline pNF1-MUT on 1L CDK4/6i and endocrine therapy had a median PFS below typical responses expected in clinical practice. A link between NF1 loss and CDK4/6i resistance was supported by in vitro experiments in HR+ breast cancer cells. NF1 deletion was accompanied by activation of ERK and AKT, therefore, future directions include investigating alternative or combination treatment strategies targeting the MAPK and/or PI3K/AKT pathways in these tumors. *MRL and RCP contributed equally. ABH and SAW are co-senior authors. Citation Format: Maxwell Lloyd, M Rosario Chica-Parrado, Todd Knepper, Chang-Ching Lin, Emily Podany, Christine Walko, Fabiana Napolitano, Caroline Weipert, Jiemin Liao, Arielle Medford, Lianne Ryan, Jennifer Keenan, Nicole Zhang, Shiyuan Liu, Gerburg Wulf, Katherine Clifton, Cynthia Ma, Hyo Han, Leif Ellisen, Aditya Bardia, Carlos Arteaga, Ariella Hanker, Seth Wander. A bedside-to-bench translational analysis demonstrates that NF1 alterations promote CDK4/6 inhibitor (CDK4/6i) resistance in hormone receptor-positive (HR+) metastatic breast cancer (MBC) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-23-09.

Abstract PO2-04-01: Predictors of exceptional response to first line HER2-targeted therapy for metastatic breast cancer

Abstract Background HER2-targeted therapies have transformed the trajectory of HER2-positive (HER2+) metastatic breast cancer (MBC), with a subgroup of responders remaining on first line (1L) therapy for many years (yrs). Despite these promising outcomes, the paradigm remains palliative, with some patients (pts) receiving therapy indefinitely. Opportunities to interrupt therapy are controversial and anecdotal in the setting of a limited understanding of long-term responders and lack of predictive biomarkers. Methods We identified prevalent pts with HER2+ MBC seen and consented at Dana-Farber Cancer Institute between 2010 and 2023, regardless of the original date of MBC diagnosis. Exceptional responders (ExRes) were pts without evidence of progressive disease (PD) 3 yrs from initiation of 1L therapy for MBC. Conventional responders (ConRes) were pts who experienced PD within 3 yrs of 1L treatment initiation. We compared clinicopathological characteristics and treatment patterns between ExRes and ConRes using Chi-square or Wilcoxon test. We analyzed median time to treatment switch due to PD (TTS-PD) – i.e., time from metastatic diagnosis to 1L treatment end due to PD - and overall survival, via the Kaplan-Meier method and with a landmark analysis at year 3 (Y3). Our primary aim was to identify predictors of exceptional response to 1L anti-HER2 therapy. Results Of 635 pts with HER2+ MBC, we identified 147 ExRes and 370 ConRes and excluded 118 pts due to follow up ≤ 3 yrs and no PD events. Median follow up was 7.1 yrs (IQR 5.5-11.0) for ExRes and 7.1 yrs (IQR 4.0-11.4) for ConRes. Median age at MBC diagnosis was 50.7 yrs (range 21.9-91.9) for ExRes and 49.8 yrs (26.9-82.3) for ConRes. ExRes presented more often with de novo MBC than ConRes (52.1 vs 30.6%, p< 0.0001). On metastatic samples, more ExRes than ConRes had HER2 3+ tumors by immunohistochemistry (IHC) (93.7 vs 81.0%, p=0.002), whereas the proportion of ER-positive disease was similar between the two groups (45.6 vs 53.4%, p=0.1). Most pts received (neo)adjuvant anti-HER2 agents in both groups (62.5 vs 72.7%, p=0.1). More ExRes than ConRes (55.8 vs 42.7% p=0.007) received 1L chemotherapy (CT) plus trastuzumab (H)/pertuzumab (P). Alternative 1L treatments were CT plus H (26.5 vs 25.7%), H +/- P +/- endocrine therapy (8.2 vs 10.5%), T-DM1 (2 vs 9.2%), tyrosine kinase inhibitors-based regimens (7.5 vs 10.8%). For pts with recurrent MBC, disease-free interval was longer for ExRes than ConRes (median 4.7 vs 3.4 yrs, p=0.01). Visceral involvement at MBC relapse was similar for ExRes and ConRes (78.2 vs 77.8%, p=0.9). Brain metastases at any timepoint were less frequent among ExRes than ConRes (42.9 vs 55.1%, p=0.01). Among ExRes, 70 (47.6%) pts experienced PD after Y3, with a median TTS-PD of 4.6 (4.1-5.1) yrs. In a landmark analysis at Y3, the 2-year TTS-PD was 68.5% (95% CI: 59.8%-75.7%) (5 yrs from treatment start), and 4-year overall survival was 86.5% (95% CI: 78.1%-91.9%) (7 yrs from treatment start). ConRes received a median of 5 (1-19) treatment regimens for MBC, with a median 1L TTS-PD of 12 (10.8-13) mo. A total of 89 (60.5%) ExRes and 214 (57.8%) ConRes underwent tumor sequencing. Data comparing genomic features between ExRes and ConRes will be presented. Conclusions In this prospective cohort, 28% of pts with HER2+ MBC had exceptional response to 1L anti-HER2 therapy. Consistent with prior data, ExRes present more frequently with de novo disease and HER2 IHC 3+ tumors. In our cohort, ExRes had a median follow-up of 7.1 years and 52.4% never experienced PD. Although a significant proportion of pts with HER2+ MBC derive long-term benefit from anti-HER2 therapy, the treatment paradigm remains palliative, and it is unknown whether biomarkers may reliably predict exceptional response and guide future treatment. Ongoing work will explore whether genomic features vary between ExRes and ConRes. Citation Format: Stefania Morganti, Tianyu Li, Katheryn Santos, Melissa Hughes, Nolan Priedigkeit, Yvonne Li, Marla Lipsyc-Sharf, Gregory Kirkner, Janet Files, Julie Kasparian, Elizabeth Grant, Gunjan Gupta, Giuseppe Curigliano, Sara Tolaney, Andrew Cherniack, Nabihah Tayob, Nancy Lin, Heather Parsons. Predictors of exceptional response to first line HER2-targeted therapy for metastatic breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-04-01.

Abstract PO4-04-03: Empowering Oncologists to Develop Individualized Management Strategies for HER2+ Metastatic Breast Cancer: Findings from a Quality Improvement Initiative

Abstract Background: Rapidly evolving evidence in the treatment of metastatic HER2+ metastatic breast cancer (MBC) can present challenges in aligning practice with the latest clinical data and guideline recommendations. In this ongoing quality improvement initiative, we identify and address real-world challenges healthcare professionals (HCPs) face in individualizing treatment plans, adverse event management, and patient-centered care for HER2+ MBC. Methods: From 9/2022 to 12/2022, 22 HCPs who treat patients with breast cancer (BC) along with 52 patients with HER2+ MBC from 2 large US community oncology clinics completed tethered surveys assessing practice patterns, challenges, and attitudes related to individualized and patient-centered care for HER2+MBC. Patient charts (n=100) were audited to assess current practice patterns and to track changes over time. Inclusion criteria included a confirmed HER2+ MBC diagnosis, prescription for two or more lines of HER2+ breast cancer treatment, and ≥ 1 visit in the one-year chart abstraction period. HCPs participated in audit-feedback sessions to assess site-specific challenges and gaps and developed action plans for improvement. Follow-up chart audits and HCP surveys will evaluate changes in practice patterns 6 months after the educational intervention. Results: The most frequently reported HCP challenges included coordination of care (41%) and individualizing treatment plans (32%). The most frequently reported patient challenges included feeling confident in treatment plan (30%) and being unable to meet work or home responsibilities (22%). In tethered surveys, there were discordant findings between patient and HCP perceptions related to goals for treatment, patient education, and patient-centered care. For example, 82% of HCPs reported often or always asking patients about treatment preferences, but only 8% of patients reported their doctor asked. While HCPs overwhelmingly thought surviving as long as possible was their patients’ top goal (82%), patients reported their top goals for treatment were improving quality of life (57%) and controlling symptoms (41%). Additionally, while HCPs thought patients had the most difficulty managing nausea/vomiting (68%) and diarrhea (59%), patients reported they have the most difficulty managing fatigue (46%) and hair loss (44%). Baseline chart audits highlighted several areas for improvement in guideline-aligned care, including treatment selection, sequencing, and supportive care. Based on identified gaps, providers developed and implemented action plans, such as increasing use of patient navigators, referring patients for palliative care at time of diagnosis, improving multidisciplinary team-based approaches, and implementing tools and resources to stay up-to-date on clinical evidence and guidelines. Full findings from baseline surveys and chart audits will be presented, along with follow-up surveys and chart audits to measure impact. Conclusions: Through this QI initiative, we identified gaps in individualized, guideline-aligned, patient-centered care for patients with HER2+ MBC, and HCPs developed and are implementing action plans for improvement. The methods and findings from this initiative demonstrate key opportunities to improve outcomes for patients with HER2+ MBC in community oncology clinics. Citation Format: Reshma Mahtani, Erika Hamilton, Ilona Dewald, Chelsie Anderson, Jeffrey Carter, Cherilyn Heggen, Kelly McKinnon. Empowering Oncologists to Develop Individualized Management Strategies for HER2+ Metastatic Breast Cancer: Findings from a Quality Improvement Initiative [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-04-03.

Abstract PO1-10-03: Prevalence of and Factors Associated with Food Insecurity and Other Adverse Social Determinants of Health Among Breast Oncology Patients

Abstract Background: Social determinants of health (SDOH), the non-medical factors that influence health status, have a profound impact on breast cancer (BC) outcomes and contribute to survival disparities. Food insecurity (FI), defined as a lack of consistent access to adequate food resources, is a modifiable SDOH associated with treatment disruptions, medication nonadherence, and decreased quality of life. To identify at-risk patients and inform future interventions, we implemented SDOH screening of patients seen in breast oncology clinic at our urban academic medical center. Methods: Screening was conducted through an 8-item questionnaire on the electronic patient portal. The questions covered FI, housing and transportation challenges, and emergency department (ED) visits. We conducted a retrospective analysis of SDOH data collected among patients scheduled for a breast oncology appointment between 11/1/22 and 5/25/23. Any level of food hardship or concern constituted a positive FI screen. Descriptive statistics were used to determine the prevalence of FI and other SDOH, to assess differences in FI rates by age, race/ethnicity, and clinical stage, and to compare characteristics of food-insecure vs food-secure patients. We also conducted a multivariable logistic regression analysis to estimate the odds ratio (OR) and 95% confidence interval (CI) associated with sociodemographic/clinical factors and FI. Results: A total of 2,585 patients were seen in our breast oncology practice, of which 1,189 (46.0%) were screened for SDOH, including 41.2% non-Hispanic White (NHW), 9.6% non-Hispanic Black (NHB) and 21.0% Hispanic patients. Among patients who responded to each SDOH question, 15.5% (146/940) reported some level of FI; 8.7% (84/962) were unable to pay their rent or mortgage on time; for 5.8% (57/989), lack of transportation interfered with their treatment. The FI rate differed significantly by race and ethnicity: 4.5% of NHW, 15.2% of NHB, and 41.8% of Hispanic patients reported FI (p< 0.001). In multivariable analysis, NHB and Hispanic patients also had significantly higher odds of FI compared to NHW patients (OR=3.68, 95% CI=1.7-7.7, p< 0.001 for NHB and OR=15.0, 95% CI=8.8-27.1, p< 0.001 for Hispanic patients). Patients with metastatic disease had higher rates of FI compared to other breast oncology patients (23.6% vs 14.8%, p=0.048), and a metastatic BC diagnosis was associated with over twice the odds of FI (OR=2.18, 95% CI=1.1-4.2, p=0.02). Among food-insecure patients, 41.1% were unable to pay their rent or mortgage on time and 22.6% reported transportation difficulties interfering with treatment (vs 2.6% and 2.4%, respectively, for food-secure patients (p< 0.001)). Compared to food-secure patients, those who were food-insecure had significantly higher rates of self-reported ED visits in the past 12 months: 18.8% vs. 33.6% reported at least 1 ED visit, respectively, and 5.2% vs. 16.4% reported multiple ED visits, respectively (p< 0.001). Conclusions: In this analysis of SDOH data among patients seen in breast oncology clinic, FI was the most common social health risk reported, with nearly a quarter of patients with metastatic BC reporting FI. Racial/ethnic minorities were also at considerably higher risk for FI. ED utilization was significantly higher among food-insecure patients. Targeted interventions to reduce FI in at-risk populations are warranted to improve clinical and healthcare utilization outcomes. Sociodemographic and Clinical Characteristics and Other Reported Social Determinants of Health Among Food-Secure vs Food-Insecure Patients Citation Format: Claire Sathe, David DeStephano, Anita Gul, Melissa Beauchemin, Justine Kahn, Melissa Accordino, Katherine Crew, Ngozika Emezienna, Dawn Hershman. Prevalence of and Factors Associated with Food Insecurity and Other Adverse Social Determinants of Health Among Breast Oncology Patients [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-10-03.

Abstract PO3-20-02: Olaparib front line therapy with endocrine therapy in locally advanced unresectable or in metastatic breast cancer: OFELIA TRIAL

Abstract INTRODUCTION: Currently, patients with recurrent or metastatic hormone-sensitive breast cancer are treated with endocrine therapy (ET) in combination with cyclin inhibitors, as it has been shown to improve both overall survival and progression-free survival. However, it has been observed that patients with gBRCA1 or gBRCA2 mutations, who receive treatment with endocrine therapy and CDK4/6 inhibitors, have lower OS and lower PFS compared to those without mutations. These findings could be due to the presence of higher cyclin E mRNA levels, which encode the protein that stimulates CDK2 activity provoking a resistance to CDK4/6 inhibitors. Having this said, the use of PARP inhibitors a potential first-line therapeutic option in combination with endocrine therapy could be an option to be re evaluated. JUSTIFICATION: PARP inhibitors (iPARP) are recommended in international guidelines as second-line palliative treatment and also as adjuvant management in the case of Olaparib. The use of iPARP is approved only as a second-line treatment in HER2 hormone-sensitive breast cancer, according to the results of the EMBRACA and OlympiAD clinical trials. However, these two clinical trials were not designed to evaluate its effectiveness as first-line palliative treatment. Given that patients with gBRCA mutations have lower overall survival when administered cyclin inhibitors (iCDK 4/6) + Endocrine therapy (ET) compared to those without mutations, it is necessary to reevaluate the use of iPARP as first-line palliative treatment in conjunction with ET, with the expectation of achieving a similar objective response rate and progression-free survival. OBJECTIVE: To Determine the ORR in patients with recurrent or metastatic hormone-sensitive HER2-negative breast cancer managed with PARP inhibitors + Endocrine therapy. HYPOTHESIS: The use of PARP inhibitors in combination with endocrine therapy will have an objective response rate of 60% or higher in both early stages and advanced disease. METHODOLOGY: Phase 2 open-label, multicenter clinical trial. Study Population: Cohort : All pre- or postmenopausal patients with a diagnosis of recurrent or metastatic hormone-sensitive HER2-negative breast cancer with gBRCA1 and/or gBRCA2 mutation. Sample: The inclusion of patients will be based on meeting the inclusion criteria. We plan to achieve an ORR of at least 60% with an acceptable minimum of 40%. Assuming a one-sided alpha level of 0.05 and statistical power of 80%, a two-stage Simon design was used to calculate the required sample size. In the first stage, a minimum of 23 patients is assumed, of which 14 patients need to achieve the desired response rate to proceed to the second stage. In the second stage, an additional 28 patients will be added to obtain a total sample size of 51 patients. The objective response rate will be evaluated using RECIST v1.1 criteria at 8 weeks after initiating treatment, with continued assessment during the first year, followed by assessments every 12 weeks during the second and third year, and then every 24 weeks until progression or toxicity. EXPECTED RESULTS: PARP inhibitors + Endocrine therapy will have a similar ORR as reported with cyclin inhibitors + Endocrine therapy, as well as a benefit in progression-free survival. Citation Format: Carlos Arturo González Núñez, Paula Cabrera-Galeana, Juan Enrique Bargalló Rocha, Rafael Vazquez-Romo, Sergio Aguilar-Villanueva, Alexandra Garcilazo, Areli Velazquez-Martinez, Andrea Maliachi, Ruben Rodriguez. Olaparib front line therapy with endocrine therapy in locally advanced unresectable or in metastatic breast cancer: OFELIA TRIAL [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-20-02.

Abstract PO2-04-04: Trastuzumab deruxtecan for the treatment of patients with HER2-positive breast cancer with brain and/or leptomeningeal metastases: an updated overall survival analysis using data from a multicenter retrospective study (ROSET-BM)

Abstract Background: ROSET-BM (UMIN000044995) was a multicenter, retrospective chart review study of patients (pts) who received trastuzumab deruxtecan (T-DXd) treatment for HER2-positive (HER2+) metastatic breast cancer (MBC) with brain metastases (BM) and/or leptomeningeal carcinomatosis (LMC). Primary results (data cutoff, October 31, 2021) were presented at SABCS2022 (median progression-free survival [PFS], 16.1 months; 1-year overall survival [OS] rate, 74.9%; and median follow-up duration, 11.2 months). To confirm the long-term effectiveness of T-DXd in HER2+ MBC pts with BM and/or LMC, we conducted an updated analysis using additional 1-year follow-up data. Methods: Pts who started T-DXd treatment between May 25, 2020, and April 30, 2021, were registered for ROSET-BM. For this updated OS analysis, the extended observation period ended on October 31, 2022. OS, PFS, and time to treatment failure (TTF) were evaluated. Median survival times and 95% CIs were calculated using the Kaplan–Meier method. In addition, prespecified and exploratory subgroup analyses were performed based on patient background characteristics. Univariate and multivariate Cox proportional hazards regression models were used to evaluate baseline prognostic factors for OS. Results: 104 pts from 62 institutions were included in this updated OS analysis. Median duration of follow-up was 20.4 months. Median number of prior lines of therapy was 4 (range, 1–15). Median time from first diagnosis of MBC to first administration of T-DXd was 37.5 months. Median time from first diagnosis of BM to first administration of T-DXd was 18.9 months. The prevalence of active BM, stable BM, LMC, and unclassified (image not evaluated) was 64.4% (n=67), 11.5% (n=12), 18.3% (n=19), and 5.8% (n=6), respectively. Median OS was not reached (NR) among all pts (1-year OS rate, 74.8%; 2-year OS rate, 56.0%). Subgroup analyses showed that median OS in pts with active BM was 27.0 months (95% CI, 16.4 to NR) and that median OS was NR in pts with stable BM or LMC (2-year OS rate for pts with stable BM, 71.6%; 2-year OS rate for pts with LMC, 61.6%). The results of univariate and multivariate analyses for OS showed no relevant baseline prognostic factors. Among all pts, median PFS was 14.6 months (95% CI, 10.6–20.8). Subgroup analyses showed that in pts with active BM, stable BM, and LMC, median PFS was 13.2 months (95% CI, 10.0–20.3), NR (95% CI, 5.3 to NR), and 17.5 months (95% CI, 8.3–22.1), respectively. Among all pts, median TTF was 9.3 months (95% CI, 6.3–11.8). The most common event and adverse event leading to discontinuation of T-DXd was progressive disease (37 pts, 35.6%) and interstitial lung disease (ILD; 24 pts, 23.1%), respectively. Median time to onset of an ILD event was 5.3 months (range, 0.7–20.0). ILD was grade 1 in 14 pts (13.5%), grade 2 in 3 pts (2.9%), grade 3 in 5 pts (4.8%), grade 4 in 2 pts (1.9%), and grade 5 in 0 pts. The Table summarizes the primary and updated results of ROSET-BM. Conclusion: The updated OS results of this retrospective chart review show that T-DXd has promising effectiveness in HER2+ MBC pts with long-term and heavily pretreated BM and LMC. This study was funded by Daiichi Sankyo Co., Ltd. Primary and updated results from the ROSET-BM study The updated results show that T-DXd has promising effectiveness in HER2+ MBC pts with long-term and heavily pretreated BM and LMC. Citation Format: Takashi Yamanaka, Naoki Niikura, Takahiro Nakayama, Mitsugu Yamamoto, Kazuo Matsuura, Kenichi Inoue, Sachiko Takahara, Hironori Nomura, Shosuke Kita, Miki Yamaguchi, Tomoyuki Aruga, Nobuhiro Shibata, Akihiko Shimomura, Yuri Ozaki, Shuji Sakai, Daisuke Takiguchi, Takehiko Takata, Armin Bastanfard, Kazuhito Shiosakai, Junji Tsurutani. Trastuzumab deruxtecan for the treatment of patients with HER2-positive breast cancer with brain and/or leptomeningeal metastases: an updated overall survival analysis using data from a multicenter retrospective study (ROSET-BM) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-04-04.

Abstract RF02-06: AVIATOR/TBCRC045: A randomized phase II study of vinorelbine (N) + trastuzumab (H) alone or combined with avelumab (A) +/- utomilumab (U) in patients (pts) with HER2+ metastatic breast cancer (MBC) (NCT03414658)

Abstract Background: Chemotherapy (chemo) + H is standard of care therapy for pts with refractory HER2+ MBC. It is unknown whether the addition of immune checkpoint inhibitor (ICI) or a 4-1BB agonist (U) improves efficacy of standard chemo + H for this population. Methods: Eligible pts had HER2+ MBC previously treated with H, pertuzumab (P), and T-DM1. Pts previously treated with N or ICI were excluded. 100 pts were randomized 1:2:2 to tx with NH, NHA, or NHAU. ER status and presence of liver metastases were stratification factors. The original co-primary objectives were to compare progression-free survival (PFS) of (1) NHA vs NH; and (2) NHAU vs NHA. In 2021, due to discontinuation of clinical development of U, an unplanned interim futility analysis reviewed by IDMC led to closure of NHAU and randomization of the final 13 pts to NH or NHA. For the comparison of NH vs NHA, with 60 pts randomized (20 vs 40) there was 88% power for a log-rank test to detect improvement in median PFS (mPFS) from 2 to 4 mos with one-sided alpha of 0.1. Corresponding 2-sided 80% confidence intervals (CI) were reported for the stratified Cox model hazard ratios (HR), along with stratified one-sided log-rank p-value. Secondary endpoints included overall response rate (ORR), duration of response (DOR), and safety/tolerability. Results: 100 pts were randomized from 7/2018-3/2023, and 97 pts started tx on trial: 18 NH, 45 NHA, and 34 NHAU (prior to its closure). Pts were 99% female, with median age 54 yrs (range 26-78 yrs); 70% White, 14% Black, and 8% Asian; 7% were Hispanic. 66% of pts had hormone receptor-positive tumors, and 76% had visceral metastases. All pts were previously treated with H, P, and T-DM1, and 17% had prior trastuzumab deruxtecan. 63% of pts had received ≥3 lines of HER2 tx for MBC (range 1-13 lines), and median interval from MBC diagnosis to randomization was 32 mos (interquartile range 22-61 mos). mPFS and ORR results are shown in the Table. One patient remained progression-free on tx at analysis. NHA was associated with a statistically significant improvement in PFS compared to NH (HR=0.56 (80% CI 0.37-0.86, p=0.04)). No difference in PFS was observed between NHAU vs NHA (HR=1.20 (80% CI 0.84-1.73) as final estimate after closure of NHAU for futility). Of 9 pts with confirmed responses in NHA arm, 3 pts had DOR >12 mos. Grade 3-4 treatment-emergent adverse events (AEs) were similar by tx: 61% NH, 62% NHA, and 67% NHAU. There were no grade 5 treatment-related AEs. Immune-related all grade AEs in the A-containing arms (n=79 safety-evaluable pts treated with A) included: AST increase (n=15), ALT increase (n=9), hyper/hypothyroidism (n=8), adrenal insufficiency (n=2), and pneumonitis (n=1), of which two events were grade 3 (adrenal insufficiency and AST increase) and none were grade 4. Only 3 pts (1 in NHA; 2 in NHAU) stopped trial tx for unacceptable AEs. Required baseline and on-tx biopsies were performed; PD-L1 and TIL data will be presented. Conclusions: This trial demonstrated significant improvement in PFS with addition of avelumab to NH among pts with heavily pre-treated HER2+ MBC. 4-1BB agonist did not improve PFS. To our knowledge, this is the first randomized trial to report results of chemo/H +/- ICI in HER2+ MBC. Further investigation of ICI with chemo/H for pts with refractory HER2+ MBC is warranted, and the potential predictive value of immune biomarkers should be explored. *one-sided stratified log rank test p-value Citation Format: Adrienne Waks, Ruichao Shi, Meredith Regan, Chau Dang, Cesar Santa-Maria, Kelly Westbrook, Vandana Abramson, Rashmi Murthy, Rita Nanda, Hope Rugo, Amy Clark, Candace Mainor, Claire Dees, Valentina Hoyos, Kathy Miller, Erica Stringer-Reasor, Natasha Hunter, Sun Young Oh, Michelle DeMeo, Amanda Okpoebo, Erin Elias, Busem Kurt, Nancy Lin, Mothaffar Rimawi, Antonio Wolff, Elizabeth Mittendorf, Shom Goel, Sara Tolaney, Sherene Loi, Ian Krop. AVIATOR/TBCRC045: A randomized phase II study of vinorelbine (N) + trastuzumab (H) alone or combined with avelumab (A) +/- utomilumab (U) in patients (pts) with HER2+ metastatic breast cancer (MBC) (NCT03414658) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr RF02-06.